Ionophores are lipid-soluble organic molecules that disrupt cellular transmembrane potential by rendering biologic membranes permeable to specific ions. They include mobile-carriers that complex with metal cations and channel-formers that insert into the membrane to form hydrophilic pores. Although mobile-carriers possess anticancer properties, investigations on channel-formers are limited. Here, we used the channel-forming ionophore gramicidin A to study its effects on the growth and survival of renal cell carcinoma (RCC) cells. RCC is a histologically heterogeneous malignancy that is highly resistant to conventional treatments. We found that gramicidin A reduced the in vitro viability of several RCC cell lines at submicromolar concentrations (all IC50 < 1.0 μmol/L). Gramicidin A exhibited similar toxicity in RCC cells regardless of histologic subtype or the expression of either the von Hippel-Lindau tumor suppressor gene or its downstream target, hypoxia-inducible factor-1α. Gramicidin A decreased cell viability equal to or greater than the mobile-carrier monensin depending on the cell line. Mechanistic examination revealed that gramicidin A blocks ATP generation by inhibiting oxidative phosphorylation and glycolysis, leading to cellular energy depletion and nonapoptotic cell death. Finally, gramicidin A effectively reduced the growth of RCC tumor xenografts in vivo. These results show a novel application of gramicidin A as a potential therapeutic agent for RCC therapy.
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http://dx.doi.org/10.1158/1535-7163.MCT-13-0445 | DOI Listing |
Astrobiology
January 2025
Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro, Bari, Italy.
Agent-based simulations are set to describe the early biotic selection of oligomers made of monomers of different chirality. The simulations consider the spatial distribution of agents and resources, the balance of biomass of different chirality, and the balance of chemical energy. Following the well-known Wald's hypothesis, a disadvantage is attributed to the change in chirality along the biochemical sequence.
View Article and Find Full Text PDFBiomolecules
December 2024
Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, 31/4 Leninskiy Prospekt, 119071 Moscow, Russia.
Gramicidin A is a natural antimicrobial peptide produced by . Its transmembrane dimer is a cation-selective ion channel. The channel is characterized by the average lifetime of the conducting state and the monomer-dimer equilibrium constant.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2024
Phenome Research Center, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China.
Pancreatic cancer is one of the most lethal cancers, with a 5-year overall survival rate of less than 10%. Despite the development of novel therapies in recent decades, current chemotherapeutic strategies offer limited clinical benefits due to the high heterogeneity and desmoplastic tumor microenvironment (TME) of pancreatic cancer as well as inefficient drug penetration. Antibody- and nucleic acid-based targeting therapies have emerged as strong contenders in pancreatic cancer drug discovery.
View Article and Find Full Text PDFCell Death Dis
December 2024
Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death globally. Also, there is still a lack of effective therapeutic strategies for CRC patients owing to a poor understanding of its pathogenesis. Here, we analysed differentially expressed genes in CRC and identified CPNE7 as a novel driver of colorectal tumorigenesis.
View Article and Find Full Text PDFEur J Med Chem
February 2025
Department of Chemistry, School of Physics, Chemistry and Earth Sciences, The University of Adelaide, Adelaide, South Australia, 5005, Australia. Electronic address:
The rise of multidrug-resistant bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA), necessitates the development of new antibacterial therapies. Antimicrobial peptides offer a promising alternative to conventional antibiotics due to their unique mechanisms of action. Gramicidin S exhibits potent bactericidal activity against S.
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